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PubMed2000

Role of dopamine in the behavioural actions of nicotine related to addiction.

Experimental impairment of dopamine function by 6-hydroxydopamine lesions or by dopamine receptor antagonists shows that dopamine is involved in nicotine's discriminative stimulus properties, nicotine-induced facilitation of intracranial self-stimulation, intravenous nicotine self-administration, nicotine conditioned place-preference and nicotine-induced disruption of latent inhibition. Therefore, nicotine depends on dopamine for those behavioural effects that are most relevant for its reinforcing properties and are likely to be the basis of the abuse liability of tobacco smoke. On the other hand, in vivo monitoring studies show that nicotine stimulates dopamine transmission in specific brain areas and in particular, in the shell of the nucleus accumbens and in areas of the extended amygdala. These effects of nicotine resemble those of a reward like food except that nicotine-induced release of dopamine does not undergo single-trial, long-lasting habituation. It is speculated that repeated non-habituating stimulation of dopamine release by nicotine in the nucleus accumbens shell abnormally facilitates associative stimulus-reward learning. Acute effects of nicotine on dopamine transmission undergo acute and chronic tolerance; with repeated, discontinuous exposure, sensitization of nicotine-induced stimulation of dopamine release in the nucleus accumbens core takes place while the response in the shell is reduced. It is speculated that these adaptive changes are the substrate of a switch from abnormal incentive responding controlled by consequences (action-outcome responding) into abnormal habit responding, triggered by conditional stimuli and automatically driven by action schemata relatively independent from nicotine reward. These two modalities might coexist, being utilized alternatively in relation to the availability of tobacco. Unavailability of tobacco disrupts the automatic, implicit modality of abnormal habit responding switching responding into the explicit, conscious modality of incentive drug-seeking and craving.

Behavior, Addictive↗

PubMed2006

Influence of abstinence and conditions of cocaine access on the reinforcing strength of cocaine in nonhuman primates.

The development of addiction is marked by a transition from recreational to uncontrolled drug use. Investigators modeling this phenomenon in rodents observed increases in cocaine self-administration when conditions of drug access were altered as well as after abstinence. The present studies were designed to extend this research to nonhuman primates by examining whether the reinforcing strength of cocaine could be altered by changing conditions of cocaine availability or by introducing abstinence periods. Rhesus monkeys self-administered cocaine (0.03-0.3 mg/kg per injection) under a progressive-ratio (PR) schedule of reinforcement in evening sessions, with the number of injections earned serving as a measure of reinforcing strength. Alterations in the reinforcing strength of cocaine were assessed after additional access to cocaine under a fixed-ratio (FR) schedule was provided in morning sessions and following various periods of abstinence (3, 7 and 14 days) from regimens of self-administration that resulted in a range of cocaine intakes. Under baseline PR conditions, the maximum number of cocaine injections increased dose-dependently, peaking when 0.3 mg/kg per injection cocaine was available. No increases in the reinforcing strength of cocaine were observed under any condition. In contrast, a statistically significant decrease in the reinforcing strength of cocaine was observed following 14 days of abstinence under one condition. These results fail to support the views that increasing access to cocaine or abstinence enhances the reinforcing strength of cocaine.

Animals↗

PubMed1993

Higher and longer stress-induced increase in dopamine concentrations in the nucleus accumbens of animals predisposed to amphetamine self-administration. A microdialysis study.

Individual vulnerability to the reinforcing effects of drugs appears to be a crucial factor in the development of addiction in humans. In the rat, individuals at risk for psychostimulant self-administration (SA) may be identified from their locomotor reactivity to a stress situation such as exposure to a novel environment. Animals with high locomotor responses to novelty (high responders, HR) acquire amphetamine SA, while animals with low responses (low responders, LR) do not. In this study we examined by microdialysis whether stress-induced extracellular dopamine (DA) concentrations in the nucleus accumbens differed between these two groups of animals. This neurotransmitter was studied because it is thought to be involved in the reinforcing effects of psychostimulants. Furthermore, previous studies have shown that HR animals have a higher basal DOPAC/DA ratio in the nucleus accumbens and higher extracellular concentrations of dopamine in this structure in response to cocaine. The stress procedure used in this experiment consisted of a 10 min tail-pinch. HR animals displayed a higher and longer stress-induced changes in DA concentrations than the LR group. Regression analysis showed that stress-induced changes in DA levels accounted for 75% of the variance observed in the locomotor response to a novel environment. Since higher DA activity in the nucleus accumbens has been reported in animals in which the propensity to psychostimulant SA is induced by brain lesions or life events, this biochemical modification may be one neurobiological substrate of the predisposition to acquire psychostimulant self-administration.

Amphetamine↗

PubMed2005

Abstinence-induced changes in self-report craving correlate with event-related FMRI responses to smoking cues.

Drug cues have been shown to activate brain regions involved in attention, motivation, and reward in addicted users. However, as studies have typically measured responses in only one state (ie drug abstinence), it is unclear whether observed activations represent amplification by abstinence or stable responses. Thus, the present study was designed to evaluate the stability of event-related responses to visual drug cues in dependent smokers (n=13) using event-related functional magnetic resonance imaging measures. Imaging was conducted following smoking as usual and following overnight abstinence, and self-reported craving measures were obtained before, during, and after scanning. Analysis of hemodynamic response (HDR) amplitudes in each of 13 regions of interest revealed larger responses to smoking compared to control cues in ventral anterior cingulate gyrus (vACG) and superior frontal gyrus. Responses to smoking cues in these and all other regions revealed no effects of abstinence/satiety, thus supporting the notion that cue-elicited brain responses are relatively stable. However, while the abstinence manipulation did not alter group-level responses to smoking cues, at the individual level, abstinence-induced changes in craving (abstinence minus satiety) were positively correlated with changes in HDR amplitude to smoking cues in frontal regions including left inferior frontal gyrus, left vACG, and bilateral middle frontal gyrus. These results suggest that brain responses to smoking cues, while relatively stable at the group level following short-term abstinence, may be modulated by individual differences in craving in response to abstinence-particularly in regions subserving attention and motivation.

Adult↗

PubMed2003

Cue-induced behavioural activation: a novel model of alcohol craving?

RATIONALE: Alcohol-associated cues elicit craving in human addicts but little is known about craving mechanisms. Current animal models focus on relapse and this may confound the effect of environmental cues. OBJECTIVES. To develop a model to study the effects of environmental cues on alcohol consumption in animals not experiencing withdrawal or relapse. METHODS: Rats were trained to orally self-administer an alcohol (5% w/v)/saccharin (0.2%) solution 30 min a day for 20 days. After stable responding on a free choice between alcohol/saccharin and water, rats were exposed to 5, 10 or 15 min of alcohol-associated cues or 5 min of non-alcohol associated cues. The effect of a 5-min cue was measured after a 10-day break from training or pre-treatment with 0.03, 0.1 or 1 mg/kg naltrexone. RESULTS: Rats given 5 min of alcohol-associated cues responded significantly more on the active lever (26% increase) and consumed more alcohol as verified by increased blood alcohol levels (8.9 mM versus control 7.5 mM). Ten or 15 min of cues did not change alcohol consumption and 5 min in a novel environment decreased response by 66%. After a 10-day break in training, 5 min of alcohol-associated cues still increased alcohol consumption (29% increase) and the cue effect could be dose-dependently blocked by naltrexone (143% decrease at 0.03 mg/kg). CONCLUSIONS: Cue-induced behavioural activation was specific to alcohol cues, reproducible, persistent and could be blocked by naltrexone, and its correlation with human self-report of craving makes it a potentially useful model for studying alcohol craving.

Alcohol Drinking↗

PubMedDate not supplied

Video lottery terminal access and gambling among high school students in Montréal.

BACKGROUND: Gambling is a risky behaviour that involves uncertain financial outcomes, can be addictive, and has been associated with strongly adverse social and public health outcomes. We wanted to assess whether socio-economic and gambling-related-opportunity environments of neighbourhoods affected the uptake of video lottery terminal (VLT) gambling among Montréal youth. METHODS: Spatial and statistical analyses were conducted to examine geographical patterns of neighbourhood socio-economic conditions, VLT sites (n=407), and high school locations (n=305) within the Montréal Census Metropolitan Area (CMA). VLT concentration within high school neighbourhoods was measured to examine how the number of VLT opportunities varies according to socio-economic status of the school neighbourhood. A student survey was analyzed using logistic regression analysis to explore the role of individual (student) characteristics and environmental (neighbourhood) characteristics in predicting the VLT gambling behaviours reported among a sample (n=1206) of high school students. RESULTS: Video lottery gambling opportunities are more prevalent near schools located in socio-economically deprived neighbourhoods compared with schools located in more affluent neighbourhoods. The principal individual risk factors for VLT gambling were shown to be male sex, peer VLT-use, substance use, as well as the after-school routines of youth. INTERPRETATION: The spatial distribution of VLTs reflects local geographies of socio-economic disadvantage and may have a pronounced impact on students attending schools in lower income neighbourhoods, especially those with individual risk factors. Efforts to reduce gambling-related public health costs may want to take into account the socio-spatial distribution of gambling opportunities, particularly in the local environments that youth frequent.

Adolescent↗

PubMed1991

The addiction to negativity.

In this paper, we have described a type of resistance that has attracted increasing psychoanalytic attention in recent years. Patients exposed to intense negativity during early life may develop an addiction to negative experience as adolescents and adults, and this may constitute a central organizing feature of their personality. In almost all patients, however, some moments of negativity may be observed. We have traced the developmental origins of an attachment to negativity, drawing especially on psychoanalytic investigations of preoedipal pathology. Manifestations and derivatives of early negativity include anhedonia, attachment to physical pain, fear of success, masochism, deprivation of self and others, and negative voyeurism. In discussing the dynamic functions of negativity, we place particular emphasis on two motives: the patient's desires for revenge against early objects that have been a source of deprivation and frustration; and the defensive function of negativity in helping to express as well as ward off dangerous wishes to merge with the object. Deviant forms of autoerotism are likely to be used by these patients to deal with the reactivation of early experiences of neglect and rejection. When negativity is used as a defense or method of relating to others it can lead to a severe disruption of the psychotherapeutic relationship. We have reviewed suggestions for the management of extreme negativity in treatment. Resolution of the therapist's countertransference reactions, especially induced feelings of frustration, rage, and helplessness, is crucial. Emphasis also has been placed on the patient's desires for revenge against self and object, and the manner in which these may be understood and eventually resolved. Only when patient and therapist begin to investigate the adaptive functions of extreme negativity can this pathological symptom be resolved and the patient's awareness of self and sense of autonomy be enhanced.

Adolescent↗

PubMed2004

Study of the behavioural responses related to the potential addictive properties of MDMA in mice.

We investigated several behavioural responses induced by repeated administration of MDMA in mice that could be related to its potential abuse liability. Mice treated with MDMA at the dose of 10 mg/kg displayed a significant conditioned place preference with respect to saline treated controls, while lower doses (0.3, 1.0, 3.3 mg/kg) had no effect. The development of physical dependence was also investigated. Mice were treated with MDMA (10 mg/kg) twice daily for 5 days. On day 6, following a single administration of MDMA mice received the following monoaminergic antagonists: metergoline (0.1 and 1 mg/kg), ritanserin (0.25 and 1 mg/kg), timolol (2 and 10 mg/kg), prazosin (0.25 and 1 mg/kg), SCH 23390 (0.05 and 0.25 mg/kg), raclopride (0.1 and 0.5 mg/kg) or vehicle, and several somatic manifestations of withdrawal were evaluated for 45 min. Metergoline induced paw tremor, face rubbing, as well as an increase in locomotor activity in mice chronically treated with MDMA. Ritanserin, and timolol induced only paw tremor, while SCH 23390 and raclopride did not produce any somatic manifestation indicative of abstinence. The possible modification of the rewarding properties of MDMA (10 mg/kg) by the monoaminergic antagonists producing the most relevant somatic signs of withdrawal namely, metergoline (0.1 and 1 mg/kg) and timolol (2 and 10 mg/kg) were tested in the conditioned place preference paradigm. Results showed that metergoline did not significantly modify the rewarding properties of MDMA, whereas only the highest dose of timolol was able to decrease MDMA reward. No signs of dopaminergic neurotoxicity were observed following chronic treatment with MDMA as revealed by [(3)H] mazindol binding. The possible motivational and affective components of the withdrawal syndrome were assessed in the suppression of operant responding for food, the conditioned place aversion, and the lit/dark paradigms. Results showed that the somatic symptoms observed were not accompanied by any aversive/dysphoric or anxiogenic-like behaviours. These results reveal the rewarding properties of MDMA in mice, and suggest that chronic MDMA administration does not induce classical manifestations of physical dependence in mice.

Animals↗

PubMed2005

Excessive alcohol consumption and dependence on amphetamine are associated with parallel increases in subjective ratings of both 'wanting' and 'liking'.

AIM: One of the tenets of the incentive sensitization theory of drug addiction is that 'as drugs come to be wanted more and more, they often come to be liked less and less'. The aim of this study was to test whether this assumption holds true. Specifically, the study aimed to test the hypothesis that in non-clinical samples, dependence on amphetamines and excessive alcohol use are associated with increased 'wanting' but decreased 'liking' for the drug. DESIGN, SETTING AND PARTICIPANTS: In two studies, the Desires for Alcohol Questionnaire (DAQ) was administered to 380 recreational drinkers, and the Desires for Speed Questionnaire (DSQ) and the Leeds Dependence Questionnaire (LDQ) were administered to 174 amphetamine users. Scales were derived from the DAQ and DSQ representing craving, on one hand, and positive and negative reinforcement on the other hand. Craving and positive reinforcement were taken as measures of alcohol or amphetamine 'wanting' and 'liking', respectively. FINDINGS: Scores on all three DAQ scales increased monotonically as a function of the extent of alcohol consumption. Scores on all three DSQ scales increased monotonically as a function of dependence, as measured by the LDQ. 'Liking' for amphetamine was unrelated to time since the drug was last taken. (These data were not available for alcohol.) CONCLUSIONS: The finding that 'wanting' increased as a function of dependence on amphetamine or level of consumption in the case of alcohol is as predicted by the incentive sensitization theory, but the finding that 'liking' also increased as a function of dependence or excess is the opposite of the predicted effects While not refuting the incentive sensitization theory directly, the study questions the validity of one of the tenets of the theory.

Adolescent↗

PubMed2003

Subjective effects of the nicotine lozenge: assessment of abuse liability.

RATIONALE: A nicotine lozenge was developed as a novel smoking cessation aid. Abuse liability, which in this context refers to use by novices not addicted to tobacco, may be expected to be low for the lozenge due to the relatively slow route of nicotine absorption. However, its resemblance to commercially marketed lozenges and its palatability, intended to increase medication compliance, may increase its abuse liability, especially among younger individuals. OBJECTIVES: The present study evaluated the abuse liability of the nicotine lozenge. Effects of the lozenge on cigarette craving were also measured. METHODS: Subjective and physiological effects of the nicotine lozenge were tested in healthy adult smokers ( n=12, 22-55 years old); a group of younger subjects ( n=12, 18-21 years) was also included to allow for assessment of abuse liability of the lozenge in young adults specifically. Amphetamine and a confectionery lozenge were included in the study conditions as positive controls for abuse liability and palatability, respectively, and nicotine gum was included to allow for comparison with a marketed oral nicotine replacement product with low abuse liability. RESULTS: The nicotine lozenge did not increase ratings of traditional abuse liability predictors (good effect, like effect, MBG scale of the ARCI), while amphetamine significantly increased ratings on these measures. The lozenge dose dependently decreased craving for cigarettes after 70 min of abstinence, but only in the older group. Palatability of the lozenge was rated lower than a confectionery lozenge, but not lower than nicotine mint gum. CONCLUSIONS: Results suggest that the nicotine lozenge has low abuse liability, both in adults and young adults. The lozenge reduces craving to smoke, although craving reduction may not apply to young adults (18-21 years). Subjective effects of the lozenge are consistent with utility as a smoking cessation aid and are comparable to those of nicotine gum.

Adolescent↗

PubMed2001

Neural activity related to drug craving in cocaine addiction.

BACKGROUND: Crack cocaine dependence and addiction is typically associated with frequent and intense drug wanting or craving triggered by internal or environmental cues associated with past drug use. METHODS: Water O 15 positron emission tomography (PET) studies were used to localize alterations in synaptic activity related to cue-induced drug craving in 8 crack cocaine-dependent African American men. In a novel approach, script-guided imagery of autobiographical memories were used as individualized cues to internally generate a cocaine craving state and 2 control (ie, anger and neutral episodic memory recall) states during PET image acquisition. RESULTS: The mental imagery of personalized drug use and anger-related scripts was associated with self-ratings of robust drug craving or anger, and comparable alterations in heart rate. Compared with the neutral imagery control condition, imagery-induced drug craving was associated with bilateral (right hemisphere amygdala activation greater than left) activation of the amygdala, the left insula and anterior cingulate gyrus, and the right subcallosal gyrus and nucleus accumbens area. Compared with the anger control condition, internally generated drug craving was associated with bilateral activation of the insula and subcallosal cortex, left hippocampus, and anterior cingulate cortex and brainstem. A brain-wide pixel-by-pixel search indicated significant positive and negative correlations between imagery-induced cocaine craving and regional cerebral blood flow (rCBF) in distributed sites. CONCLUSIONS: The collected findings suggest the craving-related activation of a network of limbic, paralimbic, and striatal brain regions, including structures involved in stimulus-reward association (amygdala), incentive motivation (subcallosal gyrus/nucleus accumbens), and anticipation (anterior cingulate cortex).

Adult↗

PubMed2006

Subjective responses to initial experience with cocaine: an exploration of the incentive-sensitization theory of drug abuse.

AIMS: This study investigated the relationship between positive and negative subjective responses at the time of initial cocaine use with adult cocaine dependence and life-time use rates. Psychostimulant pre-exposure, regular smoking or stimulant treatment before initiation were examined to explore the incentive sensitization theory of addiction. PARTICIPANTS: A total of 202 adult participants who had tried cocaine on at least one occasion were studied prospectively from childhood into adulthood. The cocaine-initiated group included 89 who met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for attention deficit hyperactive disorder (ADHD) and 113 age-matched controls. DESIGN: Five childhood and three adulthood interviews provided data on ages of initiation into cocaine and life-time use of cocaine from ages 16-40 years. Correlations of each subjective response and analyses of variance (ANOVAs) of cocaine 'liking' and 'wanting' with DSM-III-R cocaine dependence and life-time use provided support for the validity of the measures. ANOVA provided evidence of the effect of psychostimulant pre-exposure on 'liking' and 'wanting'. Logistic regression modeled the prediction of dependence and life-time use with the independent variables of 'liking' and 'wanting', psychostimulant pre-exposure and participant characteristics. RESULTS: When cocaine was first tried, 'liking' and 'wanting' were significant predictors of cocaine dependence and life-time use. Mean 'liking' or 'wanting' responses did not differ by participant characteristics. Those who were pre-exposed by regular smoking or stimulant treatment had higher 'liking' and 'wanting' scores; but participants who were pre-exposed by both stimulant treatment and regular smoking reported the lowest liking and the highest wanting responses, consistent with the incentive sensitization theory. Logistic regression showed that the 'liking' and 'wanting' responses increased significantly the odds of DSM-III-R cocaine dependence and life-time use. CONCLUSION: In this sample, subjective 'liking' and 'wanting' measured risk for cocaine abuse.

Adult↗

PubMed1999

Dopaminergic mechanisms mediating the incentive to seek cocaine and heroin following long-term withdrawal of IV drug self-administration.

RATIONALE: The neurobiological mechanisms underlying the persistence of drug craving in detoxified addicts are still poorly understood. OBJECTIVE: The present study was designed to evaluate dopaminergic mechanisms in drug-seeking behaviour following long-term (>3 weeks) extinction of IV drug self-administration in rats. METHODS: To that end, we studied the effects of direct and indirect dopamine (DA) agonists on reinstatement of previously extinguished responding for heroin (50 microg/kg per injection; 14-15 daily 3-h sessions) and cocaine (500 microg/kg per injection; 10-11 daily 2-h sessions). RESULTS: In animals with a cocaine history, priming with cocaine, the selective DA reuptake inhibitor GBR-12909 and the DA D2 receptor agonist quinpirole resulted in robust and selective reinstatement of non-reinforced nose poking behaviour in the previously drug-paired hole. In contrast, the D1 agonist SKF-82958 failed to reinstate responding and the non-selective DA agonist apomorphine even suppressed responding in these animals. In heroin-trained rats, heroin and GBR-12909 strongly reinstated responding, whereas all direct DA agonists were ineffective. Again, the two highest doses of apomorphine decreased responding in these animals. In a parallel study, the ability of DA ligands to express behavioural sensitization in animals pretreated with amphetamine or morphine was evaluated. Interestingly, all agonists that reinstated responding in the present study caused expression of locomotor sensitization and vice versa. CONCLUSIONS: The differences between direct and indirect agonists indicate a clear, but complex, involvement of DA in drug-seeking behaviour long after detoxification. Moreover, the results show an important role of D2 receptor activation in the persistence of cocaine- but not heroin-seeking behaviour. Finally, the results from both studies suggest a relationship between drug-induced reinstatement and drug hyperresponsiveness in long-term abstinent rats.

Animals↗

PubMedDate not supplied

Naltrexone versus acamprosate: one year follow-up of alcohol dependence treatment.

Naltrexone and acamprosate reduce relapse in alcohol dependence. They have not yet been compared in a published trial. The aim of this study was to compare the efficacy of these compounds in conditions similar to those in routine clinical practice. Random allocation to a year of treatment with naltrexone (50 mg/day) or acamprosate (1665-1998 mg/day) was made in 157 recently detoxified alcohol-dependent men with moderate dependence (evaluated using the Addictions Severity Index and Severity of Alcohol Dependence Scale). All were patients whom a member of the family would accompany regularly to appointments. Alcohol consumption, craving and adverse events were recorded weekly for the first 3 months, and then bi-weekly, by the treating psychiatrist who was not blinded. At 3-monthly intervals, investigators who were blinded to the treatment documented patients' alcohol consumption based on patients' accounts, information given by the psychiatrists when necessary, and reports from patients' families. Serum gamma-glutamyltransferase (GGT) was also measured. Efforts were made to sustain the blindness of the investigators. The same investigator did not assess the same patient twice. The integrity of the blindness was not checked. There was no difference between treatments in mean time to first drink (naltrexone 44 days, acamprosate 39 days) but the time to first relapse (five or more drinks in a day) was 63 days (naltrexone) versus 42 days (acamprosate) (P = 0.02). At the end of 1 year, 41% receiving naltrexone and 17% receiving acamprosate had not relapsed (P = 0.0009). The cumulative number of days of abstinence was significantly greater, and the number of drinks consumed at one time and severity of craving were significantly less, in the naltrexone group compared to the acamprosate group, as was the percentage of heavy drinking days (P = 0.038). More patients in the acamprosate than the naltrexone group were commenced on disulfiram during the study. Naltrexone patients attended significantly more group therapy sessions, though this could not explain their better outcome. There were non-significant trends for the naltrexone group to comply better with medication, to stay in the study longer, and to show greater improvement over baseline in serum GGT.

Acamprosate↗

PubMed2026

Mapping and measuring addiction recovery: Recommended protocols through the PHENX toolkit.

BACKGROUND: Addiction "recovery" has served as a positive conceptual basis for major public health frameworks, communication strategies, and policies. With greater research interest and increasing explication of the recovery construct a multitude of measures have emerged, prompting a need to reach consensus on recommendations to enable better data harmonization and cross-study syntheses. The PhenX (consensus measures for Phenotypes and eXposures) Toolkit (www.phenxtoolkit.org) is a freely accessible catalog of validated protocols designed to promote data comparability across clinical, epidemiological, and genomic research, yet contained no recovery-specific measures. METHOD: In 2024, a Substance Use and Recovery Working Group (SURWG) followed a well-established and detailed PhenX consensus process to identify and recommend protocols suitable for recovery research. Protocols were chosen based on criteria including recovery specificity, brevity, psychometrics, scoring simplicity, and non-proprietary access. The broader scientific community (12 national/regional organizations) provided feedback (respondent N = 86) on the SURWG's preliminary recommendation which was incorporated into final decisions. RESULTS: In 2025, the PhenX Toolkit released 15 new recommended protocols across three broad recovery elements: 1. Biopsychological (post-acute withdrawal; craving), 2. Socio-ecological (social relationships;social network characteristics; substance use goal; recovery identity; recovery capital), 3. Treatment and recovery services (Treatment and Recovery Services Use; Satisfaction; and Happiness in Recovery; Mutual-Help). CONCLUSIONS: This PhenX Toolkit SURWG process resulted in a new Substance Use Recovery Specialty Collection of recommended protocols with specific multidimensional applicability. As such, they provide the field with pre-vetted tools that researchers can employ with some confidence to enhance empirical efficiency and return on national research investment.

Humans↗

PubMed2005

The duration and correlates of addiction and treatment careers.

While addiction is increasingly recognized as a chronic condition, little information is available on the actual duration of addiction and treatment careers. The purpose of this study was to estimate the duration and correlates of years between (a) first use and at least a year of abstinence and (b) first treatment admission and at least one year of abstinence. Data are from 1,271 of 1,326 (96%) people recruited from a stratified sequential sample of admissions to publicly funded treatment programs in a large metropolitan area. Participants were interviewed at 6, 18, 24, 36, 48, and 60 months post-intake. With an average age at the referent intake of 35 (SD = 8) years, the sample is 59% female, 87% African American, 7% Hispanic, and 5% white. The most common dependence diagnoses were for cocaine (64%), alcohol (44%), opioids (41%), and/or marijuana (14%). Using lifetime substance use and treatment histories collected at intake and subsequent treatment utilization recorded during follow-up interviews, we conducted survival analysis to estimate the time from first use and first treatment until people reported 12 months of abstinence or died (with people still using, in treatment, or dead at the last follow-up treated as right censored). During the three years after intake, 47% reached at least 12 months of abstinence. The median time from first to last use was 27 years. The median time from first treatment episode to last use was 9 years. Years to recovery were significantly longer for males, people starting use under the age of 21 (particularly those starting under the age of 15), people who had participated in treatment 3 or more times, and for people high in mental distress. The exploratory results suggest that multiple episodes of care over several years are the norm and that rather than thinking of multiple episodes in terms of "cumulative dosage," it might be better thought of as further evidence of chronicity and that we need to develop and evaluate models of longer term recovery management.

Adolescent↗

PubMed2003

Effect of HD-23, a potent long acting cocaine-analog, on cocaine self-administration in rats.

RATIONALE: "Agonist" therapy for drug addiction proposes that a long acting analog, with similar properties to the abused substance might serve as a useful therapeutic agent. HD-23 is a very long acting tropane analog that displays a neurochemical profile similar to cocaine. OBJECTIVE: To determine, using self-administration procedures and three different schedules of reinforcement, the effect of HD-23 on rate of cocaine intake (fixed ratio), the effect of HD-23 on the motivation to respond (progressive ratio) and the time course of HD-23 pretreatment (discrete trials). METHODS: Male Sprague-Dawley rats were implanted with chronically indwelling intravenous cannulae and trained to self-administer cocaine (1.5 mg/kg per infusion) on a fixed ratio schedule. After a stable baseline was established, separate groups of rats ( n=6-8) were given access to various doses of cocaine (0.37, 0.75, 1.5 or 3.0 mg/kg per injection) on a fixed ratio schedule during daily 3-h sessions, or to various doses of cocaine (0.18, 0.37, 0.75, 1.5 mg/kg per injection) on a progressive ratio schedule during daily 5-h sessions. A separate group of rats ( n=10) was tested using a discrete trials procedure; animals were given the opportunity to self-administer cocaine (1.5 mg/kg per injection) during 10-min trials which were initiated every 20 min throughout the day/night cycle. RESULTS: On the FR schedule, pretreatment with HD-23 (1.0 mg/kg) decreased the rate of cocaine intake. HD-23 shifted the dose-response curve on the PR schedule to the left. On the discrete trials schedule, animals displayed a circadian pattern of drug intake; pretreatment with HD-23 significantly increased cocaine intake for about 8 h during the light phase when the probability of responding would otherwise have been very low. Animals pretreated with HD-23 displayed a high probability of cocaine self-administration for about 14 h. CONCLUSIONS: The results are consistent with the idea that an acute pretreatment with the long-acting agonist, HD-23, augmented rather than diminished the motivation to self-administer cocaine.

Animals↗

PubMed2006

A 3-year study of addiction mutual-help group participation following intensive outpatient treatment.

BACKGROUND: Addiction-focused mutual-help group participation is associated with better substance use disorder (SUD) treatment outcomes. However, little has been documented regarding which types of mutual-help organizations patients attend, what levels of participation may be beneficial, and which patients, in particular, are more or less likely to participate. Furthermore, much of the evidence supporting the use of these organizations comes from studies examining participation and outcomes concurrently, raising doubts about cause-effect connections, and little is known about influences that may moderate the degree of any general benefit. METHOD: Alcohol-dependent outpatients (N=227; 27% female; M age=42) enrolled in a randomized-controlled telephone case monitoring trial were assessed at treatment intake and at 1, 2, and 3 years postdischarge. Lagged-panel, hierarchical linear models tested whether mutual-help group participation in the first and second year following treatment predicted subsequent outcomes and whether these effects were moderated by gender, concurrent axis I diagnosis, religious preference, and prior mutual-help experience. Robust regression curve analysis was used to examine dose-response relationships between mutual-help and outcomes. RESULTS: Mutual-help participation was associated with both greater abstinence and fewer drinks per drinking day and this relationship was not found to be influenced by gender, Axis I diagnosis, religious preference, or prior mutual-help participation. Mutual-help participants attended predominantly Alcoholics Anonymous and tended to be Caucasian, be more educated, have prior mutual-help experience, and have more severe alcohol involvement. Dose-response curve analyses suggested that even small amounts of participation may be helpful in increasing abstinence, whereas higher doses may be needed to reduce relapse intensity. CONCLUSIONS: Use of mutual-help groups following intensive outpatient SUD treatment appears to be beneficial for many different types of patients and even modest levels of participation may be helpful. Future emphasis should be placed on ways to engage individuals with these cost-effective resources over time and to gather and disseminate evidence regarding additional mutual-help organizations.

Adult↗